Despite all efforts, more people are diagnosed with hepatocellular carcinoma (HCC); the most common type of primary liver cancer and the second leading cause of cancer-related death worldwide. Multiple risk factors contribute to HCC development including chronic hepatitis (B and C) infection that accounts for 70%-90% of HCC cases by providing a permissive environment for HCC development. Other HCC risk factors include alcoholism, non-alcohol fatty liver disease, iron overload, and environmental carcinogens. Early stages of HCC show no symptoms, thus most patients are diagnosed at advanced stages. In addition, HCC exhibits a high rate of recurrence after resection or ablation; and is considerably resistant to cytotoxic chemotherapy, with a very limited number of available treatments. Thus, alternative therapeutics are well justified and are desperately needed to treat HCC.
Chemotherapy is the most common treatment of cancer patients. HCC is however, chemo-resistant, and the side-effects of chemotherapy are typically exhausting to the patient. Sorafenib is the first anti-HCC drug approved by the U.S. Food and Drug Administration. It is a multikinase inhibitor that blocks tumor cells proliferation and angiogenesis. Although sorafenib is successful in treating early and mid HCC lesions, it is not efficient in advanced HCC cases. The common side effects of sorafenib are skin toxicity, diarrhea, hypertension, and bleeding.
Natural products have long been a part of folk medicine and have been playing an instrumental role in the development of anti-cancer drugs. Thanks to their nontoxicity and low-to-no associated side effects, 40% of FDA-approved therapeutic agents are natural-based components or their derivatives. Considering their great efficacy and low toxicity, natural products have been extensively studied and introduced as a chemopreventive therapy for many diseases including cancer. Medicinal plants have been suggested for cancer prevention and therapy for several reasons; they contain nutritional and anti-tumor compounds, are able to delay or prevent cancer onset, can boost the physiological status and the immune system, and most importantly, they represent a great alternative and/or adjuvant option to conventional cancer treatments by alleviating or even averting their side effects.
Saffron (the stigmas of the flower of Crocus sativus), is increasingly gaining attention as it contains many bioactive molecules with health promoting properties; including crocin, crocetin, picrocrocin, and safranal, Previous studies have reported the anti-cancer activity of saffron and its derivatives against a wide range of cancers. While saffron's derivatives have been reported to inhibit the growth of HeLa cells, safranal has specifically been shown to exert potent anti-inflammatory, antioxidant and anti-cancer properties and was found to induce apoptosis in both alveolar human lung cancer A549, and human prostate cancer PC-3 cell lines. Despite all its anti-tumor activities, the mechanism through which safranal exerts its anti-cancer effect is yet to be fully understood.
Hence, it would be advantageous to understand the mechanism through which safranal exerts anti-cancer effects so it may be developed into an effective treatment for liver and other cancer types, either alone or in combination with chemotherapeutical agents.